title: Target-mediated protection of endogenous microRNAs in C. elegans.
abstract: MicroRNAs (miRNAs) are tightly regulated through transcriptional and posttranscriptional mechanisms, including degradation by nucleases. Here, we report that in C. elegans, target mRNAs can protect their cognate miRNAs from degradation in vivo. We show that the let-7(n2853) mutation destabilizes the mature let-7 miRNA by impairing this protection. Moreover, presence of a cognate target or depletion of the xrn-1 (XRN1) or xrn-2 (XRN2/Rat1p) exoribonucleases enforces accumulation of certain miRNA passenger (miR(∗)) strands. Thus, following biased miRNA strand loading into Argonaute, elimination of nonfunctional RNAs can further refine miRNA strand selection. Conversely, by aligning the levels of miRNAs with those of their targets, the opposing activities of mature miRNA degradation and target-mediated miRNA protection (TMMP) may enable dynamic expression of either mature strand of a pre-miRNA, and evolution of miRNAs. Thus, it seems that mRNAs are more than inert targets and function with miRNAs in a network of mutual regulation.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, CH-4002 Basel, Switzerland.
authors.forename: Saibal
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Monika
authors.initials: M
authors.lastname: Fasler
authors.forename: Ingo
authors.initials: I
authors.lastname: Büssing
authors.forename: Helge
authors.initials: H
authors.lastname: Grosshans
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D020871:RNA Stability
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; C474488:let-7 microRNA, C elegans; D005095:Exoribonucleases; C558127:XRN-1 protein, C elegans; C544213:XRN-2 protein, C elegans